Molecular Docking, Antioxidant, Anticancer and Antileishmanial Effects of Newly Synthesized Quinoline Derivatives

Due to the pressing need and adverse effects associated with the available anti-cancer agents, an attempt was made to develop the new anti-cancer agents with better activity and lesser adverse effects.

Synthetic approaches based on chemical modification of quinoline derivatives have been undertaken with the aim of improving anti-cancer agents' safety profile.

In the present study, quinoline derivatives 6-hydroxy-2-(4-methoxyphenyl) quinoline-4-carboxylic acid (M1) and 2-(4-chlorophenyl)-6-hydroxyquinoline-4-carboxylic acid (M3) were synthesized by the reaction of aldehyde and pyruvic acid. The complete reaction was indicated by thin-layer chromatography. Newly synthesized M1and M3were tested for in silico and in vitro studies.

M1 and M3 were docked against selected targets. Both the test compounds showed good affinity against all targets except the p300\CBP-associated factor target as there was no H-bond formed by M1. IC50 values of M1 and M3 against 1, 1-diphenyl-picrylhydrazyl free radical scavenging activity were 562 and 136.56ng/mL, respectively. In brine shrimp lethality assay, M1 and M3 showed IC50 value of 81.98 and 139.2ng/mL, respectively. IC50 values recorded for M1 and M3 in tumor inhibition activity were 129 and 219μg/mL, respectively. M1 and M3 exhibited concentration-dependent anti-cancer effects against human cell lines of hepatocellular carcinoma (HepG2) and colon cancer (HCT-116). Against HepG2 cells, M1 and M3 exhibited IC50 of 88.6 and 43.62μg/mL, respectively. M1 and M3 utilized against HCT-116 cell lines possessed IC50 values of 62.5 and 15.3μg/mL. M1 and M3 also showed an anti-leishmanial effect with IC50 values of 336.64 and 530.142μg/mL, respectively.

From the results of pharmacological studies, we conclude that the newly synthesized compound showed enhanced anti-oxidant, anti-cancer and anti-leishmanial profile with good yield.